Phase 3 iSCIB1+ gp100/TRP-2 DNA vaccine adds melanoma antigen targeting to PD-1/CTLA-4 blockade.

Scancell Ltd’s adaptive, multicenter Phase 3 trial randomizes adults with unresectable Stage III/IV melanoma to iSCIB1+ (a DNA “Immunobody” vaccine encoding melanoma antigens gp100 and TRP-2 to drive antigen-specific T-cell responses) or placebo, each given with standard nivolumab (a PD-1 checkpoint inhibitor) plus ipilimumab (a CTLA-4 checkpoint inhibitor). The Phase 2 SCOPE study provided the rationale for moving forward: across the combined SCIB1/iSCIB1+ cohorts receiving nivolumab + ipilimumab, ORR was 68.6% (46/67), with an 88% disease-control rate; in the HLA-selected iSCIB1+ cohort, PFS was 77% at 20 months. These were encouraging single-arm results rather than a randomized comparison, making the Phase 3 study the key test of whether adding the vaccine truly improves on nivolumab + ipilimumab alone. The study is double-blind and placebo-controlled, testing whether vaccine-primed, tumor-antigen–specific immunity can deepen or prolong responses achieved by checkpoint blockade alone, with endpoints including progression-free survival, overall survival, response rate, safety, and quality of life. Eligibility requires HLA positivity and known BRAF status, reflecting that vaccine-driven antigen presentation is HLA-restricted and that BRAF-mutant disease has an established targeted-therapy alternative. Commercially, it is a registrational attempt to turn a historically hard-to-scale modality (therapeutic cancer vaccines) into a broad first-line backbone alongside Bristol Myers Squibb’s nivo/ipi regimen. Current first-line treatment for advanced melanoma includes PD-1–based immunotherapy such as nivolumab + ipilimumab, nivolumab + relatlimab, or PD-1 monotherapy, with BRAF/MEK targeted therapy available for BRAF V600–mutant disease. This trial asks whether adding tumor-antigen vaccination can improve on the established nivo/ipi backbone.